The proposed Special Center of Research in Rheumatoid Arthritis at the University of Texas Health Science Center at Dallas will bring together 11 investigators to study the genetic and immunologic basis of rheumatoid arthritis. Six separate but interrelated areas of investigation will be initiated as part of the SCOR. The first will examine the genetic basis for rheumatoid factor production. The investigators will be Drs. P. Stastny, E. Ball and H.E. Jasin. The second project will analyze polymorphism in the structure of immunoglobulin variable region genes in patients with rheumatoid arthritis. This work will be carried out by Dr. J.D. Capra. In essence, these two projects will examine in detail the relationship of the development of rheumatoid arthritis to polymorphisms in constant region and variable region gene segments of immunoglobulin genes. A third project will examine there interrelationship of humoral and cell- mediated immunity in the development of inflammatory arthritis. This will make use of the preliminary observation that synergy in animal models of arthritis is noted when anti-collagen antibodies and T cells from adjuvant arthritis rats are administered to a naive recipient. The basis for this synergy will be examined in detail by Drs. J.D. Taurog and H.E. Jasin. The forth project will examine the cellular basis of rheumatoid arthritis and involve the efforts of Drs. Lipsky, Geppert, Roska, and Oppenheimer-Marks. This project will examine the nature of the T cell reactivity in the rheumatoid synovium including analysis of mechanisms of T cell entry into rheumatoid synovium, activation by endogenous antigen presenting cells, and finally the antigenic specificity of the T cells activated. T cell clones obtained from rheumatoid synovium will be analyzed for antigenic specificity and used to develop clonotypic antibodies. A fifth project will examine the possibility that T cells in the synovium of patients with rheumatoid arthritis are oligoclonal by examining the T cell receptor gene rearrangements expressed by clones generated from rheumatoid synovium. This work will be carried out by Drs. Duby and Roska. Finally, insights gathered from analysis of immunologic parameters in the aforementioned projects will be utilized to examine immune reactivity in patients with rheumatoid arthritis and amelioration of this reactivity by therapeutic interventions. These projects will provide a comprehensive evaluation of the genetic and immunologic basis of rheumatoid arthritis. Each is linked together intellectually, and by the numerous collaborations among the various investigations of the SCOR. It is anticipated that these projects should provide considerable new insight into the pathogenesis of rheumatoid arthritis.